Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells

Kyu Sang Park, Andreas Wiederkehr, Clare Kirkpatrick, Yves Mattenberger, Jean Claude Martinou, Piero Marchetti, Nicolas Demaurex, Claes B. Wollheim

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Mitochondria form filamentous networks that undergo continuous fission/fusion. In the pancreatic β-cells, mitochondria are essential for the transduction of signals linking nutrient metabolism to insulin granule exocytosis. Here we have studied mitochondrial networks in the insulinoma cell line INS-1E, primary rat and human β-cells. We have further investigated the impact of mitochondrial fission/fusion on metabolism-secretion coupling in INS-1E cells. Overexpression of hFis1 caused dramatic mitochondrial fragmentation, whereas Mfn1 evoked hyperfusion and the aggregation of mitochondria. Cells overexpressing hFis1 or Mfn1 showed reduced mitochondrial volume, lowered cellular ATP levels, and as a consequence, impaired glucose-stimulated insulin secretion. Decreased mitochondrial ATP generation was partially compensated for by enhanced glycolysis as indicated by increased lactate production in these cells. Dominant-negative Mfn1 elicited mitochondrial shortening and fragmentation of INS-1E cell mitochondria, similar to hFis1. However, the mitochondrial volume, cytosolic ATP levels, and glucose-stimulated insulin secretion were little affected. We conclude that mitochondrial fragmentation per se does not impair metabolism-secretion coupling. Through their impact on mitochondrial bioenergetics and distribution, hFis1 and Mfn1 activities influence mitochondrial signal generation thereby insulin exocytosis.

Original languageEnglish
Pages (from-to)33347-33356
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number48
DOIs
Publication statusPublished - 2008 Nov 28

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells'. Together they form a unique fingerprint.

  • Cite this

    Park, K. S., Wiederkehr, A., Kirkpatrick, C., Mattenberger, Y., Martinou, J. C., Marchetti, P., Demaurex, N., & Wollheim, C. B. (2008). Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells. Journal of Biological Chemistry, 283(48), 33347-33356. https://doi.org/10.1074/jbc.M806251200